PMID: 2495581Mar 1, 1989Paper

A selective decrease in the xenobiotic metabolizing activity of rat lungs by nitrogen dioxide exposures

Toxicology
Y Takahashi, T Miura

Abstract

Groups of male Wistar rats were continuously exposed to nitrogen dioxide (NO2) ranging from 1.2 to 15 ppm for 1 or 2 weeks to examine the dose-effect relationship between NO2 and the xenobiotic metabolizing activity of lung microsomes. The lung cytochrome P-450 decreased significantly after 1-week exposures to 10 and 15 ppm NO2 and showed a decreasing tendency after 2-week exposures to 6-10 ppm NO2. On the other hand, the cytochrome b5, NADPH-cytochrome P-450 reductase and NADH-cytochrome b5 reductase of lung microsomes were increased concomitant with increase in microsomal proteins during 2-week exposures to 6-10 ppm NO2. These results show that the lung cytochrome P-450 decreases preferentially upon exposure to NO2 at higher concentrations. The coumarin hydroxylase activity was the most sensitive to NO2 exposures among activities metabolizing 4 kinds of xenobiotics examined. The coumarin hydroxylase activity was decreased in a dose-dependent fashion to 67-10% of the control level by 2-week exposures to 1.2-6 ppm NO2 and became negligible at 10 ppm NO2. The 7-ethoxycoumarin O-deethylase activity was also decreased to 82-56% of the control level by 2-week exposures to 1.2-6 ppm NO2 and became a constantly reduced level at 10 pp...Continue Reading

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Citations

Dec 1, 1993·Trends in Pharmacological Sciences·P M Bach, H Bartsch
Jan 1, 1990·Toxicology in Vitro : an International Journal Published in Association with BIBRA·T Miura, Y Takahashi

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